Abstract
BackgroundWe introduced a hypometabolic convergence index (HCI) to characterize in a single measurement the extent to which a person’s fluorodeoxyglucose positron emission tomogram (FDG PET) corresponds to that in Alzheimer’s disease (AD). Apolipoprotein E ε4 (APOE ε4) gene dose is associated with three levels of risk for late-onset AD. We explored the association between gene dose and HCI in cognitively normal ε4 homozygotes, heterozygotes, and non-carriers.MethodsAn algorithm was used to characterize and compare AD-related HCIs in cognitively normal individuals, including 36 ε4 homozygotes, 46 heterozygotes, and 78 non-carriers.ResultsThese three groups differed significantly in their HCIs (ANOVA, p = 0.004), and there was a significant association between HCIs and gene dose (linear trend, p = 0.001).ConclusionsThe HCI is associated with three levels of genetic risk for late-onset AD. This supports the possibility of using a single FDG PET measurement to help in the preclinical detection and tracking of AD.
Highlights
Fluorodeoxyglucose (FDG) positron emission tomography (PET) measurements of the cerebral metabolic rate for glucose (CMRgl) provide a neuroimaging biomarker for the detection and tracking of Alzheimer’s disease (AD) [1] and for distinguishing Alzheimer’s disease (AD) from other dementias
In that the apolipoprotein E (APOE) e4 allele is the major genetic risk factor for late-onset Alzheimer’s disease (AD) [4] and the Apolipoprotein E e4 (APOE e4) gene dose is associated with a greater risk of AD and a younger age at clinical onset [5], we previously used fluorodeoxyglucose positron emission tomogram (FDG PET) in 160 cognitively normal late-middle-aged APOE e4 homozygotes, heterozygotes, and noncarriers to characterize associations between APOE e4 gene dose and lower CMRgl in precuneus, posterior cingulate, parietal, temporal, and frontal regions that are preferentially affected in patients with AD [6]
Data from a separate group of individuals participating in the Alzheimer’s Disease Neuroimaging Initiative (ADNI) [12] study, a longitudinal multisite study supported by the National Institutes of Health, private pharmaceutical companies, and nonprofit organizations, with approximately 50 medical center and university sites across the United States and Canada, was used as an independent data set to establish a template for defining patterns of regional hypometabolism associated with AD for the hypometabolic convergence index (HCI) computations
Summary
Fluorodeoxyglucose (FDG) positron emission tomography (PET) measurements of the cerebral metabolic rate for glucose (CMRgl) provide a neuroimaging biomarker for the detection and tracking of Alzheimer’s disease (AD) [1] and for distinguishing Alzheimer’s disease (AD) from other dementias (e.g. frontotemporal dementia and dementia with Lewy bodies). In that the apolipoprotein E (APOE) e4 allele is the major genetic risk factor for late-onset Alzheimer’s disease (AD) [4] and the APOE e4 gene dose (each additional copy of the e4 allele in a person’s APOE genotype) is associated with a greater risk of AD and a younger age at clinical onset [5], we previously used FDG PET in 160 cognitively normal late-middle-aged APOE e4 homozygotes, heterozygotes, and noncarriers to characterize associations between APOE e4 gene dose and lower CMRgl in precuneus, posterior cingulate, parietal, temporal, and frontal regions that are preferentially affected in patients with AD [6] In this previous study, we were able to demonstrate that APOE e4 gene dose was significantly correlated with hypometabolism in postulated brain regions.
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